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Amyotrophic lateral sclerosis (ALS) primarily is a neurodegenerative disease affecting
motor neurons of the primary motor cortex, corticospinal tract, brainstem and spinal cord.
ALS patients develop paralysis in the muscles of the extremities and die from respiratory
paralysis over a period of 3-5 years. Despite intensive research, no drug with significant
life-prolonging or therapeutic effects could be implemented more than 150 years after the
initial description. Only animal models - among them the far best characterized SOD1
G93A mouse model - made it possible to gain a deeper understanding of the
pathomechanisms of ALS and thus offer starting points for the development of new
therapies. Frequently discussed pathological processes in ALS are oxidative stress and
neuroinflammatory mechanisms. The pathological effect factor of oxidative stress served
as a therapeutic target for the treatment of SOD1-G93A mice by peritoneal insufflation of
an O3/O2 gas mixture. Ozone has a strong oxidative effect and thus influences the redox
balance. Experimental studies in which i.p. O3/O2 treatment was applied showed
modulating effects on the immune system of the respective model organisms. This led to
the hypothesis that repetitive i.p. O3/O2 treatment could attenuate the damaging
oxidative mechanisms in the ALS disease process and induce protective immune
responses in SOD1-G93A mice.
In the present work, the SOD1-G93A mouse model was used as a model organism to
characterize preventive and therapeutic O3/O2 treatment for the onset, progression, and
lifespan of animals. Percentage distributions of immune cell subpopulations in blood,
spleen and mesenteric lymph nodes during disease progression were measured by FACS
analysis. Attenuations of neurodegenerative processes in the brainstem were
documented by MRI analysis.
All results indicate the ineffectiveness of O3/O2 treatment on the course of ALS, including
disease start point, reductions in motor abilities, and life span. On the immunological level
no changes in the distribution of the immune cell subpopulations were detectable, while
MRI visible lesions in the brainstem of the SOD1-G93A mice remained unaffected by the
treatment. Only further analyses, based on the cell and tissue samples collected in this
study, will show whether O3/O2 therapy in connection with ALS disease can be regarded as a meaningful therapy option, for which it is worthwhile to carry out further research,
e.g. on the form of application, duration or time of intervention.